CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma.
Craig S SauterBrigitte SenechalIsabelle RivièreAi NiYvette BernalXiuyan WangTerence PurdonMalloury HallAshvin N SinghVictoria Z SzenesSarah YooAhmet DoganYongzeng WangCraig H MoskowitzSergio A GiraltMatthew J MatasarMiguel-Angel PeralesKevin J CurranJae ParkMichel SadelainRenier J BrentjensPublished in: Blood (2019)
High-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT) is the standard of care for relapsed or primary refractory (rel/ref) chemorefractory diffuse large B-cell lymphoma. Only 50% of patients are cured with this approach. We investigated safety and efficacy of CD19-specific chimeric antigen receptor (CAR) T cells administered following HDT-ASCT. Eligibility for this study includes poor-risk rel/ref aggressive B-cell non-Hodgkin lymphoma chemosensitive to salvage therapy with: (1) positron emission tomography-positive disease or (2) bone marrow involvement. Patients underwent standard HDT-ASCT followed by 19-28z CAR T cells on days +2 and +3. Of 15 subjects treated on study, dose-limiting toxicity was observed at both dose levels (5 × 106 and 1 × 107 19-28z CAR T per kilogram). Ten of 15 subjects experienced CAR T-cell-induced neurotoxicity and/or cytokine release syndrome (CRS), which were associated with greater CAR T-cell persistence (P = .05) but not peak CAR T-cell expansion. Serum interferon-γ elevation (P < .001) and possibly interleukin-10 (P = .07) were associated with toxicity. The 2-year progression-free survival (PFS) is 30% (95% confidence interval, 20% to 70%). Subjects given decreased naive-like (CD45RA+CCR7+) CD4+ and CD8+ CAR T cells experienced superior PFS (P = .02 and .04, respectively). There was no association between CAR T-cell peak expansion, persistence, or cytokine changes and PFS. 19-28z CAR T cells following HDT-ASCT were associated with a high incidence of reversible neurotoxicity and CRS. Following HDT-ASCT, effector CD4+ and CD8+ immunophenotypes may improve disease control. This trial was registered at www.clinicaltrials.gov as #NCT01840566.
Keyphrases
- diffuse large b cell lymphoma
- bone marrow
- high dose
- stem cell transplantation
- end stage renal disease
- positron emission tomography
- computed tomography
- newly diagnosed
- nk cells
- chronic kidney disease
- healthcare
- acute myeloid leukemia
- rheumatoid arthritis
- ejection fraction
- acute lymphoblastic leukemia
- free survival
- epstein barr virus
- cell therapy
- palliative care
- low dose
- squamous cell carcinoma
- stem cells
- risk factors
- mesenchymal stem cells
- radiation therapy
- signaling pathway
- induced apoptosis
- immune response
- peritoneal dialysis
- hiv infected
- cell proliferation
- high glucose
- atomic force microscopy
- case report
- systemic sclerosis
- locally advanced
- high resolution
- pet ct
- health insurance
- drug induced
- interstitial lung disease